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Biomedical subjects

A Anderson

Publications and source records attributed to A Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Plasma methylmalonic acid in relation to serum cobalamin and plasma homocysteine in a psychogeriatric population and the effect of cobalamin treatment.

Cobalamin deficiency seems to be a relatively common condition in psychogeriatric patients. To elucidate the diagnostic possibility of cobalamin deficiency we have in this study analysed three markers for cobalamin deficiency, plasma methylmalonic acid, plasma homocysteine and serum cobalamin, in 96 psychogeriatric patients. Patients were divided into four groups according to serum cobalamins above or below 150 pmol/l and normal (< 19.9 mumol/l) or increased plasma homocysteine. The upper reference limit (95th percentile) for plasma methylmalonic acid in 100 healthy subjects was established to 0.42 mumol/l. The mean value of methylmalonic acid was increased only in the group of patients with serum cobalamin below 150 pmol/l and increased plasma homocysteine compared to the other groups. In this group six (46%) out of 13 patients exhibited increased plasma methylmalonic acid, whereas in the other groups the frequency of increased plasma methylmalonic acid only varied from 10 to 13%. During cobalamin supplementation the most pronounced decrease of plasma methylmalonic acid also occurred in the group of patients with low serum cobalamin levels and increased plasma homocysteine. Only 39% of the initial mean value for plasma methylmalonic acid was noted after 7-10 days of cobalamin administration.

Aged↗
PubMed1997

Cytochrome oxidase is decreased in piglet hippocampus following hypoxia-ischemia.

We assessed cytochrome oxidase (CytOx) staining in sham-operated control piglets and in piglets subjected to 30 minutes of cerebral hypoxia-ischemia (H-I) plus 4 hours of reperfusion (REP). The 1-day-old piglets were sedated, anesthetized, and ventilated. Cerebral blood flows (CBFs) were quantitated using microspheres. H-I was induced by a combination of phlebotomy and cervical tourniquet; the brain was reperfused for four hours after 30 minutes of H-I. CBF was reduced during ischemia in experimental animals from 42 + 13 to 12 + 5 ml/min/100g. CytOx staining of hippocampal sections from 3 control and 3 experimental animals was compared. The staining of the stratum pyramidale neurons of the same portion of the CA1 sector in a single high power field was assessed in a blinded fashion in 4 corresponding sections from each animal, and graded from 0 = no staining to 3 = heavy staining. The results were compared using one-way analysis of variance. Cells with grade 3 staining were significantly more numerous in controls compared to H-I/REP animals (p = 0.03). There were significantly more cells with no CytOx staining in the experimental animals (p = 0.01). These findings suggest that CytOx staining in newborn piglet CA1 is a reliable method of assessing cell dysfunction after H-I.

Animals↗
PubMed1997

The neuronal nitric oxide synthase inhibitor 7-nitroindazole also inhibits the monoamine oxidase-B-catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

The neurodegenerative properties of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are thought to result from inhibition of complex I of the mitochondrial respiratory chain by the monoamine oxidase-B (MAO-B) generated 1-methyl-4-phenylpyridinium metabolite MPP+. Treatment with 7-nitroindazole (7-NI) protects rodents and baboons against MPTP's neurotoxicity, presumably as a consequence of its inhibition of neuronal nitric oxide synthase (nNOS). The results reported in the present communication, while not in conflict with the proposed role of nNOS, raise the possibility that the inhibition of MAO-B by 7-NI also may contribute to the observed neuroprotection.

Animals↗
PubMed1997

Does area of residence affect body size and shape?

OBJECTIVE: To examine whether neighbourhood or residence is associated with body size and shape (height, weight, BMI, waist circumference and waist-hip ratio). DESIGN: Analysis of data collected in fact to face interviews at the second wave of longitudinal health survey of two adult age cohorts in the West of Scotland. SETTING: Four socially contrasting urban neighbourhoods in Glasgow City, Scotland. SUBJECTS: A total of 691 subjects: 142 males and 176 females aged 40 at interview; and 167 males and 206 females aged 60 at interview. All had been resident in their current neighbourhood for at least four years. MEASUREMENTS: height, weight, BMI, waist circumference and waist-hip ratio. RESULTS: Neighbourhood of residence was significantly associated with height, BMI, waist circumference and waist-hip ratio after controlling for individual characteristics such as gender, age, social class, smoking behaviour and material deprivation (an index comprising income, housing tenure and car ownership). Individuals living in the most deprived neighbourhood were significantly shorter, and had bigger waist circumferences, waist-hip ratios and BMIs. CONCLUSIONS: If Health of the Nation targets on reducing the proportion of overweight individuals in the population are to be met, public health policy should focus on places as well as people.

Adult↗
PubMed1997

Inhibition of monoamine oxidase contributes to the protective effect of 7-nitroindazole against MPTP neurotoxicity.

The ability of 7-nitroindazole (7-NI) to protect against MPTP-induced neurotoxicity has been attributed to its inhibition of neuronal nitric oxide synthase. In the present study, 7-NI was found to counteract almost completely striatal dopamine depletion caused by a single subcutaneus injection of 20 mg/kg MPTP in mice. This effect, however, was accompanied by a significant reduction in the striatal levels of MPP+, the toxic metabolite generated via monoamine oxidase B-catalyzed MPTP oxidation. In the presence of 7-NI, a dose of 40 mg/kg MPTP produced MPP concentrations similar to those measured after treatment with 20 mg/kg MPTP alone. A comparison of neurotoxicity in these two experimental conditions (i.e., mice treated with 20 mg/kg alone versus 40 mg/kg MPTP plus 7-NI) revealed only a slight (20%), but statistically significant, protection of dopamine depletion with 7-NI. These data indicate that the mechanism by which 7-NI counteracts MPTP neurotoxicity in mice is not due solely to inhibition of neuronal nitric oxide synthase, but involves a reduction in MPP+ formation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

The effect on 24 h blood pressure control of an angiotensin converting enzyme inhibitor (perindopril) administered in the morning or at night.

OBJECTIVE: To determine the clinic and ambulatory blood pressure when the same dose of perindopril (4 mg) is administered in the morning (0900 h), or at night (2100 h), in particular, to determine whether the early morning blood pressure rise, the duration of effect and the pattern of response differed. METHODS: Twenty male patients with diastolic blood pressure 95-110 mmHg when seated and 24 h mean ambulatory diastolic blood pressure > 85 mmHg after 4 weeks' placebo were allocated randomly to be administered 4 mg perindopril at 0900 h or at 2100 h. Clinic blood pressure (with the patient seated and erect) was measured 2 and 4 weeks after the therapy had been started and ambulatory blood pressure monitoring with a SpaceLabs device was performed for 26 h during week 4. The patients then crossed over to the other time of dosage and the measurements were repeated. The study was conducted from a hospital clinic. RESULTS: The clinic analysis concerned all 20 patients but the ambulatory analysis concerned 18 patients because the ambulatory blood pressure monitor data sets were inadequate for two patients. Compliance was high (97 +/- 3%), with a suggestion that it was better with the 0900 h dose. Clinic blood pressure (with the patient seated and erect) was lower under both regimes and the blood pressure with night-time administration of perindopril tended to be lower than that with daytime administration (P = 0.05-0.10). Twenty-four-hour mean, daytime and night-time means were lower with both doses than they were with placebo and did not differ. Both regimes reduced the early morning peak blood pressure rise and the effect tended to be greater with the 2100 h dose (P = 0.05-0.10). The 0900 h dose had an effect that persisted for > 24 h but the effect of the 2100 h dose had dissipated 18 h after the dose. There was no excessive night-time fall in blood pressure with the 2100 h dose. The trough : peak ratio with the 0900 h dose was 0.86 for systolic and 0.70 for diastolic blood pressure. CONCLUSION: The early morning blood pressure rise is reduced more when 4 mg perindopril is administered at 2100 h. However, the 2100 h dose regime does not reduce blood pressure over 24 h whereas 24 h control is achieved with the 0900 h dose. In clinical practice the 2100 h dose would have been titrated to the next dose range in more patients. This study indicates that the response profile obtained with an angiotensin converting enzyme inhibitor cannot be transformed from one dose time to another automatically and that chronobiology has important effects on a drug's action.

Adult↗
PubMed1997

Sacral fractures in dogs and cats: a classification scheme and review of 51 cases.

A classification scheme for sacral fractures was based on a review of sacral fractures in 34 dogs and 17 cats. They were classified into five categories based on their radiographic appearance on standard lateral and ventrodorsal radiographs of the pelvis. Concomitant pelvic injuries were commonly observed: 32 per cent of dogs had a fracture of an ilium and 65 per cent of cats had union bilateral sacroiliac subluxation. Neurological deficits were common where the fractures traversed the spinal canal or sacral foraminae. Comparison is made between sacral fractures in dogs and cats, and humans.

Animals↗
PubMed1997

Prediction of developmental patterns through 40 months from 6- and 12-month neurologic examinations in very low birth weight infants.

This study examines whether neurologic examinations at 6 and 12 months of age can predict developmental patterns in very low birth weight infants and fullterm controls through 40 months of age. We performed neurologic examinations at 6 and 12 months; the Bayley Scales of Infant Development at 6, 12, and 24 months; and the Stanford-Binet and the McCarthy Motor scale at 40 months. The very low birth weight infants were categorized on the basis of socioeconomic status and high or low risk for early medical complications. More abnormal neurologic scores predicted greater deceleration of cognitive development for high-risk infants only. The 12-month neurologic examination predicted the degree of deceleration in motor development. Medical risk was an independent predictor of curvature of the psychomotor development curve. We conclude that neurologic examinations during the 1st year of life might be used with other factors in decision concerning referrals to early-intervention programs.

Analysis of Variance↗
PubMed1996

New proteins in the rat CYP2B subfamily: presence in liver microsomes of the constitutive CYP2B3 protein and the phenobarbital-inducible protein product of alternatively spliced CYP2B2 mRNA.

The rat CYP2B gene subfamily includes CYP2B1, CYP2B2 and CYP2B3. Translation of an alternatively spliced hepatic CYP2B2 mRNA would generate a CYP2B2 variant, CYP2B2v, having eight additional amino acid residues inserted between CYP2B2 positions 274 and 275. The presence of CYP2B3 and CYP2B2v in rat liver has yet to be demonstrated. cDNA expression vectors were obtained for CYP2B1, CYP2B2, CYP2B3 and CYP2B2v. All four proteins react with an anti-CYP2B1 antibody and can be resolved by SDS-PAGE. A CYP2B3-specific polyclonal antibody raised against an undecapeptide (SPVDPNTIDMT) from near the C-terminus of CYP2B3 detected a constitutive protein on immunoblots of rat liver microsomes, thus demonstrating that the CYP2B3 mRNA is translated in the liver. Similarly, a CYP2B2v-specific polyclonal antibody was raised against a peptide containing the eight additional amino acid residues (VSPAWMRE) predicted to be present in the CYP2B2v protein. It detected a phenobarbital- and Aroclor 1254-inducible protein in rat liver microsomes. Microsomes of Ad293 cells expressing cDNAs for CYP2B2 and CYP2B2v were used to metabolize 7,12-dimethylbenz[a]anthracene (DMBA), and the metabolites produced were compared with those generated by microsomes of cells expressing CYP2B1 cDNA. CYP2B2v had activity similar to that of CYP2B2 for DMBA metabolism. Both CYP2B2 forms preferentially catalyzed 12-hydroxylation, whereas CYP2B1 preferred 7-hydroxylation and exhibited turnover that was strongly suppressed as previously reported. These results demonstrate the existence in rat liver of two new CYP2B proteins: CYP2B3, the major constitutive CYP2B form, and CYP2B2v, which represents a rare case of non-aberrant alternative splicing among xenobiotic-metabolizing P450s.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Identification of CYP2B14P and CYP2B16P, two apparent pseudogenes in the rat cytochrome P450 2B (CYP2B) subfamily.

Cytochrome P450 2B3 (CYP2B3) is a member of the CYP2B subfamily and is present constitutively in rat liver. During cloning of the CYP2B3 gene, several variant genomic inserts were isolated, exoncontaining fragments of which were identified by hybridizing to CYP2B3 cDNA or exonic probes. Nucleotide sequence analysis of one set of variant inserts showed them to carry exon 1 and the 5'-flanking region of a gene designated CYP2B14P. The last codon of CYP2B14P exon 1 is a TAG translation stop codon, and thus CYP2B14P is a pseudogene. Three other inserts covering 34 kb of genomic sequence together carried 9 exons and the 5'-and 3'-flanking regions of the gene designated CYP2B16P. The 5'-splice site of CYP2B16P intron 1 is inactivated by the replacement of G by T in the normally invariant GT dinucleotide. Thus, CYP2B16P also has the characteristics of a pseudogene. The identification of CYP2B14P and CYP2B16P brings to at least seven the number of genes or pseudogenes shown by nucleotide sequence analysis to belong to the rat CYP2B subfamily.

Animals↗
PubMed1996

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Journal Article↗
PubMed1996

The influence of dietary folate and methionine on the metabolic disposition of endotoxic homocysteine.

We have investigated the disposition of potentially endotoxic homocysteine (Hcy) and its transsulfuration metabolite cysteine (Cys) in 98 individuals (age range 20-66 years). Our study reports on the relationship between Hcy and two important dietary factors likely to influence plasma levels of this thiol: dietary folate and dietary methionine. chi2 analysis shows a low frequency of elevated plasma Hcy at high folate intake. This frequency for Hcy >10 micromol/liter with a folate intake >350 microg/day is significant (P < 0.02). The data reflect a tendency for elevated Hcy values to be associated with low dietary folate, although many subjects with a low dietary folate also had a low plasma Hcy. Intake of dietary methionine was found to be significantly higher in males than in females (P < .0001). This may account for the looser relationship between Hcy and its transsulfuration product, Cys, in females (R2 = 0.30) compared to males (R2 = 0.73), since conversion of methionine to SAM in males would activate cystathionine beta synthase and commit excess Hcy to transsulfuration. The generally lower methionine intake of females means that more Hcy is utilized in the remethylation cycle in which methionine is produced from the de novo methyl group of 5-methyltetrahydrofolate or from the preformed methyl group of betaine. Clearly a Hcy moiety locked up in remethylation would be further removed from Cys, the end product of transsulfuration. An increasing number of studies are clarifying the relationship between Hcy, folate, and other B vitamins. However, less attention seems to be given to the influence of dietary methionine on the disposition of Hcy. The present study supports biochemical theory and indicates that more focus should be given to the effect of dietary methionine on Hcy. These findings have particular significance since even moderate increases in plasma Hcy are associated with a toxic vascular effect. Consequently the relationship between dietary folate and Hcy levels should be a factor in evaluating recommended dietary allowances for this vitamin. The simplicity of our dietary folate questionnaire also raises the possibility of a screening test in which individuals can ascertain whether their folate intake is adequate to reduce Hcy levels to a benign value.

Adolescent↗
PubMed1996

The anaesthetic action and modulation of GABAA receptor activity by the novel water-soluble aminosteroid Org 20599.

The anaesthetic profile of a novel water-soluble aminosteroid, Org 20599 [(2 beta, 3 alpha, 5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one methanesulphonate], and the ability of the compound to allosterically regulate the activity of the GABAA receptor, have been studied in comparison to the properties of established intravenous general-anaesthetic agents. Intravenously administered Org 20599 produced a rapid onset, short duration loss of the righting reflex in mice. The anaesthetic potency of Org 20599 was comparable to that of the steroids 5 alpha-pregnan-3 alpha-ol-20-one or alphaxalone, and exceeded that of propofol, thiopentone or pentobarbitone. Org 20599 and the reference anaesthetic agents allosterically displaced the binding of [35S]-t-butylbicyclophosphorothionate (TBPS) from GABAA receptors of rat-brain membranes with the order of potency: 5 alpha-pregnan-3 alpha-ol-20-one > Org 20599 > alphaxalone > propofol > thiopentone > pentobarbitone. At human recombinant alpha 1, beta 2, gamma 2L subunit-containing GABAA receptors expressed in Xenopus laevis oocytes, the anaesthetic agents produced a concentration-dependent and reversible potentiation of the peak amplitude of GABA-evoked currents. A similar positive allosteric action of Org 20599 was observed for the GABAA receptors expressed by bovine adrenal chromaffin cells maintained in culture. The rank order of potency in the aforementioned assays was identical to that determined from the displacement of TBPS binding. At concentrations greater than those required for potentiation of GABA, the anaesthetics exhibited GABA-mimetic effects with a rank order of potency that paralleled their modulatory activity. Such direct agonism varied greatly in maximal effect between compounds. The modulatory and direct agonist actions of Org 20599 were additionally confirmed utilizing rat hippocampal neurones in culture. The results indicate Org 20599 to be a potent and short-acting intravenous anaesthetic agent in mice and suggest positive allosteric regulation of GABAA receptor function to be a plausible molecular mechanism of action for the drug.

Anesthetics↗
PubMed1996

Nursing clinics in urban settings.

Decreased home care funding and the elimination of on-site clinics in elderly housing establishments by other organizations led to the creation of student- and faculty-staffed nursing clinics at Regis College. The initial two clinics, which have expanded to five in various sites, provide challenging clinical experiences for students, faculty members, and other members of the healthcare community. This article provides an overview of these clinics and examples of how they can work.

Aged↗
PubMed1996

How important is 24-hour control of blood pressure?

Control of blood pressure over the full 24-hour period is important to prevent, or allow resolution of, cardiac and vascular hypertrophy. In addition, the peak incidence of sudden death, myocardial infarction and stroke occurs at the time of the blood pressure increase associated with awakening and arising. There is at present no objective evidence that "good' 24-hour blood pressure control will improve prognosis. Once-daily therapy has created problems in hypertension management. The problem in assessing new drugs was that, in order to achieve blood pressure control before the next drug dose, excessive falls in blood pressure occurred at peak drug concentrations or excessive blood drug concentrations were produced. This led to the concept of a trough: peak ratio. This is not a unique property of a drug and if drugs have an Emax effect (i.e. the drug produces a plateau response) it is dose dependent. Interpreting a trough: peak ratio requires an understanding of the interaction between the pharmacokinetics and pharmacodynamics of a drug. The answer is to use drugs with an elimination half-life close to or greater than the dose interval (24 hours); to use drugs with an "effective' half-life close to or greater than the dose interval, which can be achieved either by modification of the pharmaceutical delivery system or by using drugs that produce a persistent effect because of physiological changes induced; or to give drugs more frequently than once a day. 24-hour blood pressure control is important and the trough: peak ratio of a drug gives a guide as to whether it can be achieved.

Antihypertensive Agents↗
PubMed1996

A study of the efficacy of felodipine given once or twice daily in the management of elderly hypertensive patients.

The use of medication given once daily in clinical practice may lead to inadequate control of blood pressure (BP) over 24 h because medication is frequently titrated at the time of peak effect. Twenty-three patients aged 65-84 completed a study in which they received placebo, felodipine 2.5 mg once daily, felodipine 2.5 mg 12-hourly, and felodipine 5 mg once daily in a randomized, double-blind crossover design. BP response was assessed in the clinic 24 h after medication and by 24 h ambulatory monitoring. The trough/peak ratio was defined as the fall in BP in the 23rd and 24th hour post dose divided by the fall in BP in the 3rd and 4th hour post dose. BP fell with all three regimes and the clinic BPs did not differ from each other but were lower than placebo. Peak BP responses from the ambulatory BP monitor recording were similar with each dose but a greater percentage of the effect was maintained prior to the morning dose with 2.5 mg 12 hourly and 5 mg once daily. Felodipine 2.5 mg once daily reduces BP and in some people this effect persists for 24 h. However if this dose is used BP should be measured prior to the dose of the drug to ensure that 24 h control is maintained. Felodipine 5 mg once daily and felodipine 2.5 mg b.d. were equally effective at maintaining control and there was no significant advantage in using the twice daily regime. If felodipine 5 mg once daily or higher doses are used BP can be titrated post dose with the knowledge that more than 75% of the effect will still be present prior to the next dose of the drug. Thus once daily felodipine extended release (ER) 5 mg or more can be used effectively to maintain BP control over 24 h in clinical practice. In some elderly patients felodipine ER 2.5 mg once daily is an adequate regime.

Aged↗